Plasma Cell Crystalline Inclusions in ALK-Negative Anaplastic Large Cell Lymphoma

IF 1.2
EJHaem Pub Date : 2025-06-26 DOI:10.1002/jha2.70080
Hiromi Kinoshita, Tsugumi Satoh, Hidekazu Kayano, Naoki Takahashi, Yasuhiro Ebihara
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引用次数: 0

Abstract

A 79-year-old woman presented with hematochezia. Endoscopic examination revealed a polyp in the rectum, and endoscopic mucosal resection was performed. The pathological diagnosis was carcinoma in adenoma, pTis (M). No further treatment was performed for this tumor. At that time, worsened hepatic dysfunction and fever were noted. A computed tomography scan showed systemic lymph nodes swelling and hepatosplenomegaly, indicating malignant lymphoma. Laboratory data showed markedly elevated soluble interleukin-2 receptor and lactate dehydrogenase levels of 48,897 U/mL (reference value: 204–587) and 3699 U/L (reference value: 124–222), respectively, which supported the diagnosis of lymphoma. Immunoglobulin levels were not elevated.

Bone marrow showed aggregations of abnormal lymphoid cells (Figure 1a), which possessed distinct nucleoli, abundant cytoplasm, and moderate to large irregularly shaped nuclei (Figure 1b). These cells were positive for CD30 (Figure 1c) and CD4 (Figure 1d), and negative for PAX-5, CD20, CD2, CD3, CD5, and CD7. Anaplastic lymphoma kinase (ALK) and Epstein–Barr virus-encoded small RNA in situ hybridization were negative. Light chain restriction was not detected by flow cytometry. Finally, a diagnosis of ALK-negative anaplastic large cell lymphoma (ALCL; clinical Stage 4) was made.

In addition to ALCL cell infiltration in bone marrow, plasma cells with crystalline inclusions, which exhibited a relatively larger, rectangular or rhomboid morphology, were found (Figure 2a–c; arrows), although the number of plasma cells were not increased (2.2%). These cells were positive for CD138 (Figure 2d), and these crystalline inclusions were negative for kappa and lambda immunoglobulins.

ALCL is a malignancy of mature T lymphocytes with expression of CD30. In a previous review of synchronous solid tumor and lymphoma, most cases involved the combination of adenocarcinoma and B-cell lymphoid lymphoma. ALCL occurring simultaneously with solid tumor is extremely rare, but there is one reported case of ductal breast carcinoma and breast-implant-associated ALCL. The relationship between rectal carcinoma in adenoma and the onset of ALCL in the present case is unknown. ALCL cells and plasma cells with inclusions were not detected in the polyp samples from the rectum of this patient.

Intracytoplasmic inclusions are occasionally seen in plasmacytoid or B-cell lymphoproliferative disorders such as multiple myeloma, but are rarely found in other diseases.

Some reports have described the detection of plasma cells around ALCL cells, but plasma cells with inclusions were not noted. The mechanism by which intracytoplasmic crystalline inclusions are produced is not well understood, but is related to the abnormal accumulation of cytoplasmic immunoglobulins secondary to disruption of the protein synthesis pathway.

In the present case, the patient's general condition was poor, so aggressive treatment for ALCL was not possible, and prednisolone was administered to treat ALCL and control inflammation. However, PSL alone was not sufficient and this situation might have exacerbated the inflammation. A cytokine storm might be triggered in response, possibly leading to increased release of inflammatory cytokines such as IL-6. As a result, immunoglobin synthesis might have been accelerated in some reactive clones of plasma cells, and cytoplasmic immunoglobulins might have abnormally accumulated.

Although the presence of plasma cells with crystalline inclusion might be coincidental, the accumulation of these reactive cases with crystalline inclusions in plasma cells may bring new insight in their relationship.

H.K. and Y.E. took the photographs and wrote the manuscript. T.S. and H.K. supported histopathological diagnosis. N.T. provided patient care. All the authors critically reviewed and approved the manuscript.

The authors have confirmed ethical approval statement is not required for this submission.

The authors declare no conflicts of interest.

The authors have confirmed that a patient consent statement is not required for this submission, as no patient-identifying data were used.

Abstract Image

alk阴性间变性大细胞淋巴瘤的浆细胞结晶包涵体
一名79岁妇女以便血表现。内镜检查发现直肠息肉,并行内镜粘膜切除术。病理诊断为腺瘤中癌,pTis (M)。未对该肿瘤进行进一步治疗。同时出现肝功能恶化和发热。计算机断层扫描显示全身淋巴结肿胀和肝脾肿大,提示恶性淋巴瘤。实验室数据显示可溶性白介素-2受体和乳酸脱氢酶水平分别显著升高48897 U/mL(参考值204-587)和3699 U/L(参考值124-222),支持淋巴瘤的诊断。免疫球蛋白水平未升高。骨髓显示异常淋巴样细胞聚集(图1a),核仁明显,细胞质丰富,细胞核大小不规则(图1b)。这些细胞CD30(图1c)和CD4(图1d)呈阳性,PAX-5、CD20、CD2、CD3、CD5和CD7呈阴性。间变性淋巴瘤激酶(ALK)和eb病毒编码小RNA原位杂交均为阴性。流式细胞术未检测到轻链限制。最后,alk阴性间变性大细胞淋巴瘤(ALCL;临床4期)。骨髓中除ALCL细胞浸润外,浆细胞中还可见结晶包涵体,其形态较大,呈矩形或菱形(图2a-c;箭头),但浆细胞数量未增加(2.2%)。这些细胞CD138呈阳性(图2d),这些结晶包涵体kappa和lambda免疫球蛋白呈阴性。ALCL是一种成熟T淋巴细胞表达CD30的恶性肿瘤。在之前关于同步实体瘤和淋巴瘤的综述中,大多数病例涉及腺癌和b细胞淋巴样淋巴瘤的合并。ALCL与实体瘤同时发生极为罕见,但有一例导管性乳腺癌和乳房植入物相关的ALCL报道。在本病例中,直肠癌合并腺瘤与ALCL发病之间的关系尚不清楚。本例患者直肠息肉标本中未检出ALCL细胞和含内含物的浆细胞。胞浆内包涵体偶尔见于浆细胞样或b细胞淋巴增生性疾病,如多发性骨髓瘤,但在其他疾病中很少发现。一些报道描述了在ALCL细胞周围检测浆细胞,但未注意到含有包涵体的浆细胞。胞浆内结晶包涵体产生的机制尚不清楚,但与蛋白质合成途径中断后继发的胞浆免疫球蛋白的异常积累有关。本例患者一般情况较差,无法对ALCL进行积极治疗,因此给予强的松龙治疗ALCL并控制炎症。然而,单靠PSL是不够的,这种情况可能会加重炎症。作为反应,细胞因子风暴可能被触发,可能导致炎症细胞因子如IL-6的释放增加。结果,免疫球蛋白的合成可能在一些反应性浆细胞克隆中加速,细胞质免疫球蛋白可能异常积累。虽然含有结晶包涵体的浆细胞的存在可能是巧合,但这些含有结晶包涵体的反应案例在浆细胞中的积累可能会对它们之间的关系带来新的认识。Y.E.拍了照片并写了手稿。T.S.和H.K.支持组织病理学诊断。N.T.提供病人护理。所有作者都严格审查并批准了稿件。作者已确认本次提交不需要伦理批准声明。作者声明无利益冲突。作者已经确认,本次提交不需要患者同意声明,因为没有使用患者身份数据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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